Antitumor effect of anti-brain derived neurotrophic factor monoclonal antibody in human multiple myeloma xenograft animal model.
This study was aimed to further explore whether brain derived neurotrophic factor (BDNF) pathway is a potential therapeutic target in multiple myeloma (MM) and whether anti-BDNF monoclonal antibody can prevent the development of this disease. The in vivo antitumor effect of anti-BDNF monoclonal antibody (McAb) on a human myeloma xenograft animal model was evaluated. The model of xenograft tumors was established in the nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice by subcutaneous injection of human myeloma cell line RPMI8226. The antibodies were injected intraperitoneally at a dose of 20 microg/mouse at day 1, 2, 3 after inoculation or at a dose of 100 microg/mouse once a week after tumors were detected. The microvascular densities in tumors were analyzed by immunohistochemistry study. The effect of anti-BDNF McAb on the proliferation of RPMI8226 cells in vitro and on endothelial cells network formation in the co-culture system were determined by using a (3)H-thymidine incorporation assay and a Matrigel network formation assay, respectively. The results showed that multiple injections of anti-BDNF McAb reduced the tumor size, decreased the microvascular density and significantly prolonged tumor-free time and survival time. Moreover, the proliferation of RPMI8226 cells was inhibited in vitro by anti-BDNF McAb, but not by the control IgG. Anti-BDNF McAb also inhibited RPMI8226-induced network formation in endothelial cells in vitro. It is concluded that anti-BDNF monoclonal antibody can inhibit cell growth and angiogenesis in subcutaneous plasmacytoma.
Wang
Ya-Dan
YD
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
Hu
Yu
Y
Huang
Jin
J
Zhang
Lu
L
Sun
Chun-Yan
CY
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000276:immunology*; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D054219:Neoplasms, Plasma Cell / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D019208:Brain-Derived Neurotrophic Factor